Evidence has accumulated that prostaglandins are involved in the pathophysiology of the skin. Intradermal injection of PGE1 and PGE2 causes inflammatory reaction with histological and biochemical changes similar to those observed in granulation tissue. Elevated levels of E and F prostaglandins have been recovered from skin perfusates in patients with allergic contact dermatitis. On the other hand, decreased synthesis of PGE2 has been associated with scaly dermatoses in the skin of EFA deficient rats and human psoriatic plaques. In our continuing investigations to elucidate the regulatory factors associated with the biosynthesis, degradation and action of PGE2 in the skin we propose: (1) To continue in our efforts to isolate and characterize other possible endogenous inhibitors of PGE2 synthesis from the skin of EFA deficient rats. Skin from these animals forms a fitting animal model for the study of abnormal keratinization process. Methods for these studies will include: (a) The in vitro incubations of skin extracts with radioactive arachidonic acid in the presence and absence of inhibitors; (b) The measurement of O2 consumed during the in vitro oxidation of arachidonic acid by dioxygenase from sheep vesicular gland, an initial and rate limiting step in the conversion of arachidonic acid to PGE2 with a Yellow Springs Oxygen Monitor equipped with a bath assembly. (2) To demonstrate the activity of a phospholipase A2 and its regulation in skin extracts incubated with lecithin labeled with C14-arachidonic acid in the Beta-position. (3) To investigate the metabolism of H3-PGE2 in skin of normal and EFA deficient animals in order to determine whether the interconversion of E2 to F2 alpha by an NADPH(NADH) dependent PGE2-9-keto reductase does increase in the skin of EFA deficient rats and in skin from normal human skin and from psoriatic plaques obtained at surgery. It is hoped that these studies will delineate some of the functional roles of prostaglandin in the pathophysiology of the skin. BIBLIOGRAPHIC REFERENCES: Lord, J. T., V.A. Ziboh and S. Warren. Prostaglandin binding to membrane preparations from rat skin. Advances in Prostaglandin and Thromboxane Res. Ed. by Samuelsson and R. Paoletti. Raven Press. New York, p. 291 (1976).